Method for preparing chiral allyl amine compound with high chemical and stereoselectivity

Abstract

The invention discloses a method for preparing a chiral allyl amine compound with high chemical and stereoselectivity. The method comprises the steps: dissolving 1,3-conjugated diene and amine in an organic solvent under the action of a metal reagent Ni(COD)2, a chiral diphosphine ligand and an acid additive, carrying out a reaction, and carrying out column chromatography separation and purification to obtain the chiral allyl amine compound. The method disclosed by the invention can be used for efficiently synthesizing the chiral allyl amine compound, is mild in reaction condition and wide insubstrate range, and has excellent regioselectivity, chemical selectivity and stereoselectivity. For an amine substrate containing two nucleophilic sites, the reaction sites can be well identified, and the ee value is as high as 99%. In addition, gram-scale amplification can be carried out in the reaction, and the catalyst load can be reduced to 1% or less. The method can also efficiently react with desloratadine and other drug molecules, and a new method is provided for derivatization of drug molecules and synthesis of complex drug molecules.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a method and application for preparing chiral allylamine compounds with high chemical and stereoselectivity. Background technique [0002] Chiral amine fragments widely exist in natural products and bioactive molecules [a) Lough, W.J.; Wainer, I.W. Chirality in Natural and Applied Science, Blackwell: Oxford, UK, 2002; b) Francotte E.; Lindner, W. Chirality in Drug Research, Wiley-VCH: Weinheim, 2006; c) Nugent, T.C. Chiral Amine Synthesis: Methods, Developments and Applications, Wiley-VCH: Weinheim, 2010]. Based on its important application value, the synthesis of chiral amines has attracted great interest and widespread attention in the field of organic chemistry [a) Li, W.; Zhang, X. Stereoselective Formation of Amines, 2014; b) Nugent, T.C.; El-Shazly, M. Adv. Synth. Catal. 2010, 352, 753-819; c) Patil, M. D.; Grogan, G.; Bommarius, A.; Yun, H. ACS Catal. 2018, 8,...

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Problems solved by technology

[0003] Transition metal-catalyzed asymmetric hydroamination of allenes, alkynes and conjugated alkenes has been reported [a) Lutete, L.M.; Kadota, I.; Yamamoto, Y.J.Am.Chem.Soc.2004,126,1622- 1623; b) Cooke, M.L.; Xu, K.; Breit, B. Angew. Chem. Int. Ed. 2012, 51, 10876-10879; c) Xu, K.; Wang, Y.H.; , B.Chem.Sci.2016,7,3313-3316; d) Athira, C.; Changotra, A.; Sunoj, R.B.J.Org.Chem.2018,83, 2627-2639; , Y.W.; Zhang, G.Z.Tetrahedron Lett.2018, 59, 347-355; f) Park, S.; Malcolmson, S. J.ACSCatal.2018, 8, 8468-8476; g) Berthold, D.; Geissler, A.G.A.; Giofre, S. ; Breit, B.Angew.Chem.Int.Ed.2019,58,9994-9997], but most of them are limited to noble metal catalysts such as Rh and Pd, and the scope of substrates is relatively narrow, and the tolerance of functional groups is poor

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